NSC-658497

NSC-658497 is an effective inhibitor of Ras-GEF, SOS1. NSC-658497 binds to SOS1, competitively suppresses SOS1-Ras interaction, and dose-dependently inhibits SOS1 GEF activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation^[1]. In Vitro: NSC-658497 (0-20 μM; 2 hours; NIH/3T3 cells) dose-dependently inhibits EGF (50 ng/mL)-stimulated Ras, but not EGFR activation^[1].
Concomitant to Ras inhibition, NSC-658497 (0-100 μM; 2 hours; NIH/3T3 cells) dose-dependently inhibited the EGF activated, Ras downstream targets ERK1/2 and AKT^[1].
Consistent with these results, NSC-658497 dose-dependently suppressed Ras signaling mediated by the overexpression of an active SOS1 mutant (W729L), originally identified in Noonan’s Syndrome, in human embryonic kidney cells^[1].
NSC-658497 dose-dependently inhibits 50 nM SOS1-cat mediated GDP/GTP nucleotide exchange upon 2 μM H-Ras (aa. 1-166) in the BODIPYFL-GDP dissociation assay (IC₅₀=15.4μM)^[1].
NSC-658497 (0-60 μM; 3 days; PC-3 and DU-145 cells) inhibits proliferation of prostate cancer cells^[1].
NSC-658497 (0-60 μM; 2 hours; PC-3 and DU-145 cells) dose-dependently inhibits Ras-GTP activity and the downstream p-ERK1/2 and p-Akt activities^[1].